The capabilities of current computer simulations provide a unique opportunity to model small-angle scattering (SAS) data at the atomistic level,
and to include other structural constraints ranging from molecular
and atomistic energetics to crystallography, electron microscopy
and NMR. This extends the capabilities of solution scattering
and provides deeper insights into the physics
and chemistry of the systems studied. Realizing this potential, however, requires integrating the experimental data with a new generation of modelling software. To achieve this, the CCP-SAS collaboration (
http://www.ccpsas.org/) is developing open-source, high-throughput
and user-friendly software for the atomistic
and coarse-grained molecular modelling of scattering data. Robust state-of-the-art molecular simulation engines
and molecular dynamics
and Monte Carlo force fields provide constraints to the solution structure inferred from the small-angle scattering data, which incorporates the known physical chemistry of the system. The implementation of this software suite involves a tiered approach in which
GenApp provides the deployment infrastructure for running applications on both st
andard
and high-performance computing hardware,
and SASSIE provides a workflow framework into which modules can be plugged to prepare structures, carry out simulations, calculate theoretical scattering data
and compare results with experimental data.
GenApp produces the accessible web-based front end termed
SASSIE-web,
and GenApp and SASSIE also make community SAS codes available. Applications are illustrated by case studies: (i) inter-domain flexibility in two- to six-domain proteins as exemplified by HIV-1 Gag, MASP
and ubiquitin; (ii) the hinge conformation in human IgG2
and IgA1 antibodies; (iii) the complex formed between a hexameric protein Hfq
and mRNA;
and (iv) synthetic `bottlebrush' polymers.